Lactic acidosis, pancreatitis and fatty liver

All nukes – d4T, ddI, abacavir, tenofovir, FTC, 3TC, AZT and hydroxyurea – have been linked to reports of lactic acidosis and/or pancreatitis. PIs and efavirenz have also been associated with pancreatitis.

Lactic acidosis

Lactic acid is a by-product formed when the body breaks down starches and sugars. Levels of lactic acid are normally carefully regulated by the liver.

Small increases in lactic acid (called hyperlactataemia) are relatively frequent, and are temporary, especially after exercise.

If they reach a higher level, there is a risk of lactic acidosis. This is a potentially fatal side effect related to nucleoside/tide analogues. It is now rarely reported.

Not only are nukes included in nearly all HIV combinations, but the symptoms of lactic acidosis are common side effects or symptoms.

Symptoms include:

• Unexplained tiredness, often severe.
• Sickness (vomiting) and nausea.
• Pain in the stomach, abdomen and/or liver.
• Unexplained weight loss.
• Difficulty breathing.
• Poor blood circulation – cold hands or feet or bluish skin colour.
• Sudden peripheral neuropathy.

Before combination therapy was available, this was only very rarely seen in HIV, and may well have been under diagnosed. Drug packaging now includes a clearer caution about this risk.

Pregnancy may be an additional risk factor for lactic acidosis when using nukes.

Lactic acidosis is diagnosed through examination, lab tests and an abdominal CT scan or liver biopsy. Although this toxicity is believed to be a result of damage to part of the cell called mitochondria, there is no simple test for determining people at highest risk.

Although lactic acid in blood can be measured, it is not clear whether high levels increase the risk of lactic acidosis. Over 50% of people showing a high reading on one result, return to normal with the confirmatory test. There appears to be no pattern between high levels and risk of severe toxicity.

Because lactic acid increases with any physical activity, confirmatory tests should be taken after complete rest for at least 20 minutes. Even going to the gym the day before may affect the results.

Treatment and monitoring

Early diagnosis is essential – and contacting your doctor you have any of the symptoms is important. HIV treatments may need to be stopped immediately depending on blood levels.

High doses of vitamin B complex with L-carnitine (both IV) until lactate levels normalise were reported in a Dutch study to improve the chances of survival.

Antioxidants may help to overcome mitochondrial toxicity and use of oral antioxidant supplements such as vitamin C, vitamin B complex, L-carnitine or co-enzyme-Q may help and are prescribed by some doctors.

There are no clear guidelines for restarting nucleoside therapy after a serious case of mitochondrial toxicity. Although caution is warranted, lack of other antiretroviral options has lead to people restarting without further toxicity.

Mitochondrial toxicity is thought to be responsible for other side effects including nerve and muscle damage.

Diagnosis and treatment

• Measure levels of lactic acid and blood pH.
• If lactic levels are more than 5 mmol and if you have symptoms or levels are over 10 mmol discontinue HIV medication immediately.
• Use of intravenous anti-oxidants: L-carnitine and vitamin B complex including thiamine, riboflavine, nicotinamide, pyridoxine, dichloracetic acid and dexpanthenol is recommended.

Pancreatitis

Pancreatitis is an inflammation of the pancreas characterised by abdominal or back pain and vomiting. It can also be alcohol induced and there is little specific treatment.

Blood tests measuring amylase lipase are usually checked to confirm a diagnosis of pancreatitis.

Pancreatitis can be fatal if not treated early, and can be prevented by stopping or changing HIV drugs.

Fatty liver

Hepatic steatosis is a medical term for ‘fatty liver’ which can develop from alcohol use, hepatitis, obesity and drug toxicity with nucleosides.

This build-up of fat in the liver can affect the way it processes fats. Hepatic steatosis often also leads to lactic acidosis, described above. People who weigh over 70kgs, especially women, may be more at risk of developing hepatic steatosis and lactic acidosis.

Ultrasonography is a sensitive, accurate, non-invasive screening tool to detect steatosis as this is not always shown in liver function tests.

Steatosis is also common in HIV-infected children. It has no impact on disease, testing or management.